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IUBMB Life Jun 2010The glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic... (Review)
Review
The glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic membranes and thus play major roles in the structure and function of those membranes. In most eukaryotic cells, PC and PE are synthesized by an aminoalcoholphosphotransferase reaction, which uses sn-1,2-diradylglycerol and either CDP-choline or CDP-ethanolamine, respectively. This is the last step in a biosynthetic pathway known as the Kennedy pathway, so named after Eugene Kennedy who elucidated it over 50 years ago. This review will cover various aspects of the Kennedy pathway including: each of the biosynthetic steps, the functions and roles of the phospholipid products PC and PE, and how the Kennedy pathway has the potential of being a chemotherapeutic target against cancer and various infectious diseases.
Topics: Amino Acid Sequence; Animals; Humans; Molecular Sequence Data; Phosphatidylcholines; Phosphatidylethanolamines; Sequence Alignment; Signal Transduction
PubMed: 20503434
DOI: 10.1002/iub.337 -
Journal of Lipid Research Jun 2008Phosphatidylcholine (PC) is made in mammalian cells from choline via the CDP-choline pathway. Animals obtain choline primarily from the diet or from the conversion of... (Review)
Review
Phosphatidylcholine (PC) is made in mammalian cells from choline via the CDP-choline pathway. Animals obtain choline primarily from the diet or from the conversion of phosphatidylethanolamine (PE) to PC followed by catabolism to choline. The main fate of choline is the synthesis of PC. In addition, choline is oxidized to betaine in kidney and liver and converted to acetylcholine in the nervous system. Mice that lack choline kinase (CK) alpha die during embryogenesis, whereas mice that lack CKbeta unexpectedly develop muscular dystrophy. Mice that lack CTP:phosphocholine cytidylyltransferase (CT) alpha also die during early embryogenesis, whereas mice that lack CTbeta exhibit gonadal dysfunction. The cytidylyltransferase beta isoform also plays a role in the branching of axons of neurons. An alternative PC biosynthetic pathway in the liver uses phosphatidylethanolamine N-methyltransferase to catalyze the formation of PC from PE. Mice that lack the methyltransferase survive but die from steatohepatitis and liver failure when placed on a choline-deficient diet. Hence, choline is an essential nutrient. PC biosynthesis is required for normal very low density lipoprotein secretion from hepatocytes. Recent studies indicate that choline is recycled in the liver and redistributed from kidney, lung, and intestine to liver and brain when choline supply is attenuated.
Topics: Animals; Cholesterol, VLDL; Choline; Homeostasis; Homocysteine; Humans; Mice; Phosphatidylcholines; Phosphatidylethanolamine N-Methyltransferase
PubMed: 18204095
DOI: 10.1194/jlr.R700019-JLR200 -
Ultrasonics Sonochemistry Jul 2023Casein (CAS), a typical protein emulsifier, has functional properties limited by its chemical structure in practical production applications. This study aimed to combine...
Casein (CAS), a typical protein emulsifier, has functional properties limited by its chemical structure in practical production applications. This study aimed to combine phosphatidylcholine (PC) and casein to form a stable complex (CAS/PC) and improve its functional properties through physical modification (homogeneous and ultrasonic treatment). To date, few studies have explored the effects of physical modification on the stability and biological activity of CAS/PC. Interface behavior analysis showed that compared to homogeneous treatment, PC addition and ultrasonic treatment could decrease the mean particle size (130.20 ± 3.96 nm) and increase the zeta potential (-40.13 ± 1.12 mV), indicating the emulsion is more stable. The chemical structural analysis of CAS showed that PC addition and ultrasonic treatment promoted changes in its sulfhydryl content and surface hydrophobicity, exposing more free sulfhydryl groups and hydrophobic binding sites, thereby enhancing its solubility and improving the stability of the emulsion. Additionally, storage stability analysis revealed that the incorporation of PC with ultrasonic treatment could improve the root mean square deviation value and radius of gyration value of CAS. These modifications resulted in an increase the binding free energy between CAS and PC (-238.786 kJ/mol) at 50 °C, leading to an improvement in the thermal stability of the system. Furthermore, digestive behavior analysis indicated that PC addition and ultrasonic treatment could increase the total FFA release from 667.44 ± 22.33 μmol to 1250.33 ± 21.56 μmol. In conclusion, the study underscores the effectiveness of PC addition and ultrasonic treatment in enhancing the stability and bioactivity of CAS, offering novel ideas for designing stable and healthy emulsifiers.
Topics: Emulsions; Phosphatidylcholines; Caseins; Ultrasonics; Emulsifying Agents
PubMed: 37267823
DOI: 10.1016/j.ultsonch.2023.106457 -
The American Journal of Clinical... Jul 2016The trimethylamine-containing nutrient phosphatidylcholine is the major dietary source for the gut microbiota metabolite trimethylamine-N-oxide (TMAO), which has been...
BACKGROUND
The trimethylamine-containing nutrient phosphatidylcholine is the major dietary source for the gut microbiota metabolite trimethylamine-N-oxide (TMAO), which has been related to cardiovascular diseases (CVDs) and mortality. Previous research suggested that the relation of TMAO with CVD risk might be stronger in diabetic than in nondiabetic populations. However, the evidence for an association of dietary phosphatidylcholine with CVD and mortality is limited.
OBJECTIVES
We aimed to examine whether dietary consumption of phosphatidylcholine, which is mainly derived from eggs, red meat, and fish, is related to all-cause and CVD mortality in 2 cohorts of US women and men. In particular, we also tested if such an association was modified by diabetes status.
DESIGN
We followed 80,978 women from the Nurses' Health Study (1980-2012) and 39,434 men from the Health Professionals Follow-Up Study (1986-2012), who were free of cancer and CVD at baseline, for mortality. Dietary intakes and potential confounders were assessed with regularly administered questionnaires. We used Cox proportional hazards models to estimate HRs and 95% CIs.
RESULTS
We documented 17,829 all-cause and 4359 CVD deaths during follow-up. After multivariate adjustment for potential confounders, including demographic factors, disease status, lifestyle, and dietary intakes, higher phosphatidylcholine intakes were associated with an increased risk of all-cause and CVD mortality. HRs (95% CIs) comparing the top and bottom quintiles of phosphatidylcholine intake were 1.11 (1.06, 1.17; P-trend across quintiles < 0.0001) for all-cause mortality and 1.26 (1.15, 1.39; P-trend < 0.0001) for CVD mortality in the combined data of both cohorts. The associations of phosphatidylcholine with all-cause and CVD mortality were stronger in diabetic than in nondiabetic participants (P-interaction = 0.0002 and 0.001, respectively).
CONCLUSION
These data suggest that higher phosphatidylcholine consumption is associated with increased all-cause and CVD mortality in the US population, especially in patients with diabetes, independent of traditional risk factors.
Topics: Adult; Cardiovascular Diseases; Cohort Studies; Diabetes Complications; Diet; Female; Humans; Male; Methylamines; Middle Aged; Phosphatidylcholines; Risk Factors; United States
PubMed: 27281307
DOI: 10.3945/ajcn.116.131771 -
IUBMB Life Sep 2011Neuronal differentiation is characterized by neuritogenesis and neurite outgrowth, processes, which are critically dependent on membrane biosynthesis, and therefore, on... (Review)
Review
Neuronal differentiation is characterized by neuritogenesis and neurite outgrowth, processes, which are critically dependent on membrane biosynthesis, and therefore, on the expression and regulation of enzymes involved in phospholipid biosynthesis. During the last decade a great effort was made to clarify where membrane lipids are synthesized, how the newly synthesized membrane components reach the membrane and are inserted during neuritogenesis and to elucidate the mechanism by which the supply of new membrane components is coordinated with the demand for growth. Phosphatidylcholine is the principal and essential component for mammalian membranes. This review updates the mechanism by which phosphatidylcholine biosynthesis takes place and how it is coordinately regulated during neuronal differentiation.
Topics: Animals; Cell Differentiation; Cell Membrane; Choline Kinase; Choline-Phosphate Cytidylyltransferase; Diacylglycerol Cholinephosphotransferase; Humans; Mammals; Models, Biological; Neurites; Neurons; Phosphatidylcholines
PubMed: 21818839
DOI: 10.1002/iub.521 -
The Journal of Biological Chemistry Dec 2021Many studies have confirmed the enzymatic activity of a mammalian phosphatidylcholine (PC) phospholipase C (PLC) (PC-PLC), which produces diacylglycerol (DAG) and...
Many studies have confirmed the enzymatic activity of a mammalian phosphatidylcholine (PC) phospholipase C (PLC) (PC-PLC), which produces diacylglycerol (DAG) and phosphocholine through the hydrolysis of PC in the absence of ceramide. However, the protein(s) responsible for this activity have never yet been identified. Based on the fact that tricyclodecan-9-yl-potassium xanthate can inhibit both PC-PLC and sphingomyelin synthase (SMS) activities, and SMS1 and SMS2 have a conserved catalytic domain that could mediate a nucleophilic attack on the phosphodiester bond of PC, we hypothesized that both SMS1 and SMS2 might have PC-PLC activity. In the present study, we found that purified recombinant SMS1 and SMS2 but not SMS-related protein have PC-PLC activity. Moreover, we prepared liver-specific Sms1/global Sms2 double-KO mice. We found that liver PC-PLC activity was significantly reduced and steady-state levels of PC and DAG in the liver were regulated by the deficiency, in comparison with control mice. Using adenovirus, we expressed Sms1 and Sms2 genes in the liver of the double-KO mice, respectively, and found that expressed SMS1 and SMS2 can hydrolyze PC to produce DAG and phosphocholine. Thus, SMS1 and SMS2 exhibit PC-PLC activity in vitro and in vivo.
Topics: Animals; COS Cells; Chlorocebus aethiops; Liver; Mice; Mice, Knockout; Phosphatidylcholines; Protein Domains; Recombinant Proteins; Transferases (Other Substituted Phosphate Groups); Type C Phospholipases
PubMed: 34774525
DOI: 10.1016/j.jbc.2021.101398 -
The Journal of Membrane Biology Oct 2022We studied the transleaflet coupling of compositionally asymmetric liposomes in the fluid phase. The vesicles were produced by cyclodextrin-mediated lipid exchange and...
We studied the transleaflet coupling of compositionally asymmetric liposomes in the fluid phase. The vesicles were produced by cyclodextrin-mediated lipid exchange and contained dipalmitoyl phosphatidylcholine (DPPC) in the inner leaflet and different mixed-chain phosphatidylcholines (PCs) as well as milk sphingomyelin (MSM) in the outer leaflet. In order to jointly analyze the obtained small-angle neutron and X-ray scattering data, we adapted existing models of trans-bilayer structures to measure the overlap of the hydrocarbon chain termini by exploiting the contrast of the terminal methyl ends in X-ray scattering. In all studied systems, the bilayer-asymmetry has large effects on the lipid packing density. Fully saturated mixed-chain PCs interdigitate into the DPPC-containing leaflet and evoke disorder in one or both leaflets. The long saturated acyl chains of MSM penetrate even deeper into the opposing leaflet, which in turn has an ordering effect on the whole bilayer. These results are qualitatively understood in terms of a balance of entropic repulsion of fluctuating hydrocarbon chain termini and van der Waals forces, which is modulated by the interdigitation depth. Monounsaturated PCs in the outer leaflet also induce disorder in DPPC despite vestigial or even absent interdigitation. Instead, the transleaflet coupling appears to emerge here from a matching of the inner leaflet lipids to the larger lateral lipid area of the outer leaflet lipids.
Topics: Sphingomyelins; 1,2-Dipalmitoylphosphatidylcholine; Lipid Bilayers; Liposomes; Phosphatidylcholines; Cyclodextrins
PubMed: 35471665
DOI: 10.1007/s00232-022-00234-0 -
Molecules (Basel, Switzerland) Jul 2023Phosphatidylcholine-specific phospholipase C (PC-PLC) is an enzyme that catalyzes the formation of the important secondary messengers phosphocholine and diacylglycerol... (Review)
Review
Phosphatidylcholine-specific phospholipase C (PC-PLC) is an enzyme that catalyzes the formation of the important secondary messengers phosphocholine and diacylglycerol (DAG) from phosphatidylcholine. Although PC-PLC has been linked to the progression of many pathological conditions, including cancer, atherosclerosis, inflammation and neuronal cell death, studies of PC-PLC on the protein level have been somewhat neglected with relatively scarce data. To date, the human gene expressing PC-PLC has not yet been found, and the only protein structure of PC-PLC that has been solved was from (PC-PLC). Nonetheless, there is evidence for PC-PLC activity as a human functional equivalent of its prokaryotic counterpart. Additionally, inhibitors of PC-PLC have been developed as potential therapeutic agents. The most notable classes include 2-aminohydroxamic acids, xanthates, ,'-hydroxyureas, phospholipid analogues, 1,4-oxazepines, pyrido[3,4-]indoles, morpholinobenzoic acids and univalent ions. However, many medicinal chemistry studies lack evidence for their cellular and in vivo effects, which hampers the progression of the inhibitors towards the clinic. This review outlines the pathological implications of PC-PLC and highlights current progress and future challenges in the development of PC-PLC inhibitors from the literature.
Topics: Humans; Type C Phospholipases; Phosphatidylcholines
PubMed: 37570610
DOI: 10.3390/molecules28155637 -
Respiratory Research Mar 2011Patients with adult respiratory distress syndrome (ARDS) and acute lung injury (ALI) have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B...
BACKGROUND
Patients with adult respiratory distress syndrome (ARDS) and acute lung injury (ALI) have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B in bronchoalveolar lavage fluid. No information is available on their turnover.
OBJECTIVES
To analyze disaturated-phosphatidylcholine and surfactant protein-B turnover in patients with ARDS/ALI and in human adults with normal lungs (controls).
METHODS
2H2O as precursor of disaturated-phosphatidylcholine-palmitate and 113C-Leucine as precursor of surfactant protein-B were administered intravenously to 12 patients with ARDS/ALI and to 8 controls. Disaturated-phosphatidylcholine and surfactant protein-B were isolated from serial tracheal aspirates, and their fractional synthetic rate was derived from the 2H and 13C enrichment curves, obtained by gas chromatography mass spectrometry. Disaturated-phosphatidylcholine, surfactant protein-B, and protein concentrations in tracheal aspirates were also measured.
RESULTS
1) Surfactant protein-B turned over at faster rate than disaturated-phosphatidylcholine both in ARDS/ALI patients and in controls. 2) In patients with ARDS/ALI the fractional synthesis rate of disaturated-phosphatidylcholine was 3.1 times higher than in controls (p < 0.01), while the fractional synthesis rate of surfactant protein-B was not different. 3) In ARDS/ALI patients the concentrations of disaturated-phosphatidylcholine and surfactant protein-B in tracheal aspirates were markedly and significantly reduced (17% and 40% of the control values respectively).
CONCLUSIONS
1) Disaturated-phosphatidylcholine and surfactant protein-B have a different turnover both in healthy and diseased lungs. 2) In ARDS/ALI the synthesis of these two surfactant components may be differently regulated.
Topics: Acute Lung Injury; Adult; Biomarkers; Bronchoalveolar Lavage Fluid; Case-Control Studies; Female; Humans; Italy; Kinetics; Male; Middle Aged; Phosphatidylcholines; Pulmonary Surfactant-Associated Protein B; Young Adult
PubMed: 21429235
DOI: 10.1186/1465-9921-12-36 -
STAR Protocols Dec 2022The plasma membrane containing cholesterol exhibits phospholipid asymmetry, with phosphatidylcholine and sphingomyelin enriched in its outer leaflet and...
The plasma membrane containing cholesterol exhibits phospholipid asymmetry, with phosphatidylcholine and sphingomyelin enriched in its outer leaflet and phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEtn) on the cytoplasmic side. We herein describe steps for bacterial expression of recombinant proteins that bind to membrane lipids, followed by affinity purification. Using fluorescence-labeled phospholipid analogs, we further detail the assay to detect flippase activity, which maintains the single-sided distribution of PtdSer and PtdEtn, in mammalian cells. For complete details on the use and execution of this protocol, please refer to Segawa et al. (2021)..
Topics: Animals; Cell Membrane; Phospholipids; Phosphatidylcholines; Biological Transport; Mammals
PubMed: 36595929
DOI: 10.1016/j.xpro.2022.101870